Depressive Symptoms Precede Cognitive Impairment in De Novo Parkinson's Disease Patients: Analysis of the PPMI Cohort

Introduction: Nonmotor symptoms, including depression, anxiety, apathy, and cognitive dysfunction, are common in Parkinson's disease (PD). Although a link between mood symptoms and cognitive impairment in PD has been theorized vis-à-vis striatal dopamine depletion, studies have been inconsistent regarding the relationship between mood symptoms and cognitive function. Inconsistencies may reflect the cross-sectional nature of previous studies. The current study examined the bidirectional longitudinal relationship between mood and cognition. Method: Data were obtained from 310 individuals newly diagnosed with PD, who were followed up to 4 years (baseline, 1st, 2nd, 3rd, and 4th annual follow-ups). Apathy, anxiety, depressive symptoms, motor severity, and neurocognitive functioning were assessed at each annual assessment. The longitudinal relationship between apathy, anxiety, depressive symptoms, and cognition was analyzed with multilevel models. Results: Over the 4-year period, more severe depressive symptoms were related to worse performance on tasks of processing speed, verbal learning, and verbal delayed recall. Additionally, there was a significant Depression × Time interaction, suggesting that individuals with more severe depressive symptoms experience more rapid declines in global cognitive functioning and verbal learning. Apathy and anxiety were not significantly related to performance in any cognitive test. Lagged models revealed that changes in depression precede declines in working memory, verbal learning, delayed verbal recall, and global cognition. Conclusion: Findings suggest depressive symptoms may be a harbinger for future cognitive decline among individuals with PD. General Scientific Summary Nonmotor symptoms such as depression, anxiety, apathy, and cognitive impairment are common in Parkinson's disease. The current study demonstrated that more severe symptoms of depression are related to worse cognitive functioning over the 4-year study period. Findings suggest that depression may be a harbinger for future cognitive decline among individuals with Parkinson's disease.